期刊
MOLECULAR BIOLOGY AND EVOLUTION
卷 26, 期 5, 页码 1055-1065出版社
OXFORD UNIV PRESS
DOI: 10.1093/molbev/msp020
关键词
protein structure; compensating mutations; structural divergence
资金
- EPSRC
- BBSRC [BB/F007620/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/F007620/1] Funding Source: researchfish
The complex constraints imposed by protein structure and function result in varied rates of sequence and structural divergence in proteins. Analysis of sequence differences between homologous proteins can advance our understanding of structural divergence and some of the constraints that govern the evolution of these molecules. Here, we assess the relationship between amino acid sequence and structural divergence. Firstly, we demonstrate that the relationship between protein sequence and structural divergence is governed by a variety of evolutionary constraints, including solvent exposure and secondary structure. Secondly, although compensatory substitutions are widespread, we find many radical size-changing mutations that are not compensated by neighboring complementary changes. Instead, these noncompensated substitutions are mitigated by alteration of protein structure. These results suggest a combined mechanism of accommodating substitutions in proteins, involving both coevolution and structural accommodation. Such a mechanism can explain previously observed correlated substitutions of residues that are distant both in sequence and structure, allowing an integrated view of sequence and structural divergence of proteins.
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